期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 100, 期 8, 页码 E1084-E1088出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2015-1530
关键词
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资金
- Swedish Research Council
- Swedish Diabetes Foundation
- Diabetes Wellness
- Diabetes Program
- Center for Innovative Medicine Senior Investigator grants at Karolinska Institutet
- Tore Nilsson Foundation
- Foundation for Gamla Tjanarinnor
- Ake Wiberg Foundation
- European Foundation for the Study of Diabetes/Lilly Program
- Novo Nordisk Foundation
- Novo Nordisk Fonden [NNF14OC0010187] Funding Source: researchfish
Context: MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. In white adipose tissue (WAT), recent studies suggest that miRNA levels are altered in various metabolic diseases, including obesity. Objective: The objective of the study was to determine whether adipocyte-expressed miRNAs altered by obesity can regulate adiponectin expression/secretion in fat cells. Design: Eleven miRNAs previously shown to be altered in obese human WAT were overexpressed in human in vitro-differentiated adipocytes followed by assessments of adiponectin levels in conditioned media. Setting: This was cohort study (n = 56) in an academic hospital. Patients: Subcutaneous WAT was obtained from nonobese and obese individuals. Interventions: There were no interventions in this study. Main Outcome Measure(s): Protein and mRNA levels of adiponectin were measured. Results: Of the 11 investigated miRNAs, three (miR-193b/-126/-26a) increased adiponectin secretion when overexpressed in human adipocytes. However, in human WAT only miR-193b expression correlated with adiponectin gene expression and homeostasis model assessment of insulin resistance. Moreover, quantitative PCR of miR-193b in both WAT and isolated adipocytes showed a significant association with serum adiponectin levels. Overexpression of miR-193b altered the gene expression of seven known adiponectin regulators. 3'-untranslated region reporter assays confirmed binding to cAMP-responsive element binding protein 5, nuclear receptor interacting protein 1, and nuclear transcription factor Y alpha. The effects of miR-193b on nuclear transcription factor Y alpha expression were confirmed at the protein level. Transfection with individual miRNA target protectors selective for nuclear transcription factor Y alpha and nuclear receptor interacting protein 1 abolished the stimulatory effect of miR-193b on adiponectin secretion. Conclusions: In human adipocytes, miR-193b controls adiponectin production via pathways involving nuclear transcription factor Y alpha and possibly nuclear receptor interacting protein 1.
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